The objectives of the proposed research are to describe in more specific detail the detrimental effects of maternal hypothyrodisim on brain maturation in their progeny and to see if these abnormalities correlate with motor function and learning ability. In addition, this study is designed to determine if the effects observed during the fetal and neonatal stages, due to maternal hypothyroidism, persist in the mature animal. Administration of growth hormone (GH) to the hypothyroid pregnant animal results in correction in the progeny of some of these detrimental effects. We will test also if the effects of maternal GH therapy are present in the mature offspring. Our previous studies have shown that fetuses and neonates of hypothyroid and GH treated hypothyroid mothers have altered thyroid function. However, inducing hypothyroidism in the neonate does not simulate maternal hypothyrodism. The fetuses of hypothyroids have reduced glycogen storage, decreased protein synthesis and hypoglycemia. Maternal GH therapy does correct these effects. The reduced protein synthesis, particularly brain glycoproteins, persists up to 30 days of age in progeny of hypothyroid but not GH-treated hypothyroid mothers. We will more precisely define these effects by measuring brain transport of amino acids, total brain pools of free amino acids, rate of synthesis of brain glycoproteins, brain DNA and RNA levels and RNA synthesis in fetuses and 5, 30 and 75 day old offspring of hypothyroid and GH-treated hypothyroid mothers. The number of synapses will be measured by determined by maze and agility strength testing in 30 and 75 day old progeny to assess the degree of permanent mental impairment. We will attempt to correlate the above factors with the endocrine status of the experimental animals by measuring serum thyroxin (T4), triiodothyronine (T3), thyroxine binding globulin (TBG), thyroid stimulating hormone (TSH) and GH in rats.